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OBJECTIVE: To determine a contemporary failed extubation rate, risk factors, and consequences of extubation failure in pediatric intensive care units (PICUs). Three hypotheses were investigated: a) Extubation failure is in part disease specific; b) preexisting respiratory conditions predispose to extubation failure; and c) admission acuity scoring does not affect extubation failure. DESIGN: Twelve-month prospective, observational, clinical study. SETTING: Sixteen diverse PICUs in the United States. PATIENTS: Patients were 2,794 patients from the newborn period to 18 yrs of age experiencing a planned extubation trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A descriptive statistical analysis was performed, and outcome differences of the failed extubation population were determined. The extubation failure rate was 6.2% (174 of 2,794; 95% confidence interval, 5.3-7.1). Patient features associated with extubation failure (p <.05) included age < or =24 months; dysgenetic condition; syndromic condition; chronic respiratory disorder; chronic neurologic condition; medical or surgical airway condition; chronic noninvasive positive pressure ventilation; the need to replace the endotracheal tube on admission to the PICU; and the use of racemic epinephrine, steroids, helium-oxygen therapy (heliox), or noninvasive positive pressure ventilation within 24 hrs of extubation. Patients failing extubation had longer pre-extubation intubation time (failed, 148.7 hrs, SD +/- 207.8 vs. success, 107.9 hrs, SD +/- 171.3; p <.001), longer PICU length of stay (17.5 days, SD +/- 15.6 vs. 7.6 days, SD +/- 11.1; p <.001), and a higher mortality rate than patients not failing extubation (4.0% vs. 0.8%; p <.001). Failure was found to be in part disease specific, and preexisting respiratory conditions were found to predispose to failure whereas admission acuity did not. CONCLUSION: A variety of patient features are associated with an increase in extubation failure rate, and serious outcome consequences characterize the extubation failure population in PICUs. [ABSTRACT FROM AUTHOR]

Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection., Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05)., Results: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation ( RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways ( RPL3, MRPL3, HLA-DMB, EEF1G , CD8A ) were associated with MODS recovery within a week., Conclusion: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome., Competing Interests: AGR, TN, and MMN: NIH/NIAID as declared in the funding statement - grant support paid to Boston Children’s Hospital. Also current CDC grant for COVID-19 work unrelated to current manuscript also paid to Boston Children’s Hospital under PI AGR. AGR also receives Royalties from UpToDate, Inc. as Section editor of Pediatric Critical Care Medicine. Honoraria: Grand Rounds presentations on MIS-C not related to current manuscript. Participation on a Data Safety Monitoring/Advisory Board: NIH Grace Study. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Medical Advisory Board for Families Fight Flu and Chair of International Sepsis Forum. JCC: additionally declares support from ALSAC for the current work. Other entities not related to the current work: U01AI150747, R01AI136514, U01AI144616; American Association of Immunologists Abstract award 2021, Patent: Methods for Treating or Reducing the Severity of a Viral Infection Publication no. WO 2021/226174 A1. MWH declared Kiadis, Licensing income, unrelated to the content of this manuscript, American Board of Pediatrics Payment, Abbive payment. Partner Therapeutics Provision of study drug, unrelated to the current manuscript, Sobi Provision of study drug, unrelated to the current manuscript. JC: NIH, paid to institution not related to this work; GLG Group payment to her, Elsevier payment made to her for work done as Associate Editor; Patent pending for Methods and compositions for treating and preventing T cell-driven diseases. BMC: Not related to current work: receives grants paid to institution from American Lung Association. Sobi Participation on a Data Safety Monitoring Board/Advisory Board. SLW: Receives royalties from UpToDate, Inc. Has grants/contracts with Pennsylvania Dept of Health not related to current manuscript. PGT: declares support from ALSAC and NIAID R01 AI154470 for the current work. Has several grants not associated with current work: NIAID 5R01AI128805-05; 1R01AI154470; NIAID 75N93019C00052; 5R01AI136514; 5R01AI35025; NIAID 5U01AI144616; NIAID U01AI150747. Royalties/licenses paid to both PGT and his institution: TCR cloning technology—Miltenyi Biotec & TCR amplification technology—Shennon Bio. Consulting fees paid to him: Johnson and Johnson, Cytoagents, Immunoscape, Shennon Bio. Payment or honoraria for lectures, presentations, or other events: Illumina—Future Genomic Advances, Yale University, CZ Biohub, PACT Pharma, UCSD, Tufts, University of Arizona, Mt. Sinai, Umass, OSU, Korean Association of Immunology, SISMID, University of Washington, MSKCC, Washington University, University of Missouri, Fred Hutch, UNM Illumina Single Cell, Cincinnati Childrens, University of Toronto, Purdue University, Iowa State University, University of Georgia. Patent: Methods for Treating or Reducing the Severity of a Viral Infection Publication no. WO 2021/226174 A1. (continued disclosures for PGT:) Support for attending meetings and/or travel: NIH Study Section, Keystone Viral Immunity, NIAID CEIRR, CEIRS and CIVIC meetings, GRC, 10X Users Symposium, Illumina Symposia, ImmunOktoberfest, Options for the Control of Influenza XI, Carghese Workshop, FOCIS, Max Planck for Complex Systems, Santa Fe Institute, AAI, Weizmann Institute, APS Society, Banff Institute, ISIRV meeting, University of Melbourne, British Society of Immunology. Stock or stock options: Shennon Bio Scientific advisory board payments. (Additional patents:) US20170304293A1 Coordinated metabolic reprogramming in response to productive viral infections; Cloning and expression system for t-cell receptors; License payments made to me and institution; Method for detecting SARS-CoV-2 infection. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Novak, Crawford, Hahn, Hall, Thair, Newhams, Chou, Mourani, Tarquinio, Markovitz, Loftis, Weiss, Higgerson, Schwarz, Pinto, Thomas, Gedeit, Sanders, Mahapatra, Coates, Cvijanovich, Ackerman, Tellez, McQuillen, Kurachek, Shein, Lange, Thomas and Randolph.)

Background: Despite advances in care of critically ill neonates, extended mechanical ventilation and tracheostomy are sometimes required. Few studies focus on complications and clinical outcomes. Our aim was to provide long-term outcomes for a cohort of infants who required tracheostomy., Methods: This study is a retrospective review of 165 infants born between January 1, 2000 and December 31, 2010 who required tracheostomy and ventilator support. Children with complex congenital heart disease were excluded., Results: Median gestational age was 27 weeks (range 22-43), and birth weight was 820 g (range 360-4860). The number of male (53.9%) and female (46.1%) infants was similar (P = .312). Infants were divided into 2 groups based on birth weight ≤1000 g (A) and >1000 g (B). Group A: 87 (57.6%) infants; group B 64 (42.4%). Overall tracheostomy rate was 6.9% (87/1345) for group A versus 0.9% (64/6818) for B (P <.001). Group A had a longer time from intubation to positive pressure ventilation independence, 505 days (range 62-1287) vs 372 days (range 15-1270; P = .011). Infants who had >1 reason for tracheostomy comprised 78.8% of the sample; 69.1% of infants were discharged on ventilators. Birth weight did not affect time from tracheostomy to decannulation (P = .323). More group A infants were decannulated (P = .023). laryngotracheal reconstruction rate was 35.8%. Five-year survival was 89%. Group B had higher mortality (P = .033). 64.2% of infants had developmental delays; 74.2% had ≥2 comorbidities., Conclusions: Tracheostomy rates were higher for extremely low birth weight infants than previously reported rates for all infants. Decannulation rates and laryngotracheal reconstruction rates were consistent with previous studies. Survival rates were high, but developmental delay and comorbidities were frequent.

Objective: Intubation is a risk factor for nosocomial sinusitis in adult intensive care patients. Sinusitis in intubated adults can be an occult cause of fever. In children, nasal intubation may increase the risk of sinusitis. No pediatric study has determined the frequency of nosocomial sinusitis in the pediatric intensive care unit setting. We hypothesized that within a subset of patients who had head computed tomography imaging 1) the incidental frequency of sinusitis in pediatric intensive care unit patients exceeds the frequency in non-pediatric intensive care unit patients, 2) the frequency of sinusitis is greater in pediatric intensive care unit patients with a tube (nasotracheal, nasogastric, orotracheal, or orogastric) compared to those without a tube, and 3) nasal tubes confer an increased risk for sinusitis over oral tubes., Design: Retrospective chart review., Setting: Independent not-for-profit pediatric healthcare system., Patients: Pediatric intensive care unit and non-pediatric intensive care unit (inpatients hospitalized on medical-surgical wards) patients referred for head computed tomography., Interventions: None., Measurements and Main Results: Computed tomography images were scored using the Lund-MacKay staging system. Sinusitis was defined as a Lund-MacKay score ≥5. A total of 596 patients were studied, 395 (66.3%) in the pediatric intensive care unit. A total of 154 (44.3%) pediatric intensive care unit vs. 54 (26.9%) non-pediatric intensive care unit patients had sinusitis (p < .001). A total of 102 of 147 (69.4%) pediatric intensive care unit patients with a tube present had sinusitis vs. 73 of 248 (29.4%) patients without a tube present (p < .001). There was no difference in sinusitis based on tube location (p = .472). Of patients with sinusitis, 51.3% (81 of 158) compared to 39.4% (89 of 226) were febrile within 48 hrs of imaging (p = .021). A younger age or the presence of a tube increased the probability of sinusitis (p < .001)., Conclusions: A total of 44.3% of our pediatric intensive care unit patients imaged for reasons other than evaluation for sinus disease had evidence of sinusitis, and 51.3% of these had fever. These findings raise the concern that sinusitis in pediatric intensive care unit patients is common and should be considered in the differential diagnosis of fever in pediatric intensive care unit patients.

Background: Various strategies to mitigate children's distress during voiding cystourethrography (VCUG) have been described. Sedation with nitrous oxide is comparable to that with oral midazolam for VCUG, but a side-by-side comparison of nitrous oxide sedation and routine care is lacking., Objective: The effects of sedation/analgesia using 70% nitrous oxide and routine care for VCUG and radionuclide cystography (RNC) were compared., Materials and Methods: A sample of 204 children 4-18 years of age scheduled for VCUG or RNC with sedation or routine care were enrolled in this prospective study. Nitrous oxide/oxygen (70%/30%) was administered during urethral catheterization to children in the sedated group. The outcomes recorded included observed distress using the Brief Behavioral Distress Score, self-reported pain, and time in department., Results: The study included 204 patients (99 nonsedated, 105 sedated) with a median age of 6.3 years (range 4.0-15.2 years). Distress and pain scores were greater in nonsedated than in sedated patients (P < 0.001). Time in department was longer in the sedated group (90 min vs. 30 min); however, time from entry to catheterization in a non-imaging area accounted for most of the difference. There was no difference in radiologic imaging time., Conclusion: Sedation with nitrous oxide is effective in reducing distress and pain during catheterization for VCUG or RNC in children.

Purpose: Nonsurgical treatment of lymphangiomas has shown limited efficacy and often carries unacceptable toxicities, demonstrating the need for a more effective, less toxic therapy., Patients and Methods: We describe two patients with lymphangiomatosis treated for 12 to 40 months with recombinant interferon-alpha., Results: Both patients demonstrated stabilization or marked improvement of disease, based on clinical and radiologic findings, with minimal toxicity., Conclusions: The favorable responses to interferon-alpha therapy in these two cases suggest that this is an effective and well-tolerated treatment for lymphangiomas in children.

Solid organ transplant provides lifesaving therapy for infants and children with otherwise terminal diseases, but it is severely limited by donor organ supply. Medical examiners perform a pivotal role in the organ procurement process by determining whether a "heartbeating cadaver" on life support is a medicolegally suitable donor. This descriptive questionnaire study assesses medical examiner practice and behavior regarding organ procurement from child abuse/homicide victims. Obtaining forensic evidence for judicial purposes and releasing organs to children awaiting transplantation are not necessarily conflicting values. Greater than 60% of medical examiners sampled would agree to release organs from abuse/homicide victims in the scenarios presented here if provided with requested information. Further confronting the origins of variable medical examiner practice in this area might result in the availability of additional solid organs for pediatric transplantation.

To assess whether underlying diagnosis affects morbidity and mortality outcomes in patients with chronic respiratory failure, we studied 55 patients with chronic respiratory failure of infancy and childhood (CRFIC). Entry criteria included patients with chronic respiratory failure due to static neurologic or neuromuscular conditions or secondary to other disease processes considered likely to improve or resolve over time. Subjects were grouped into those having chronic lung disease (CLD, n = 22), neurologic or neuromuscular diseases (NM, n = 21), or congenital abnormalities affecting the respiratory system (CA, n = 12). The average duration of follow-up was 21.3 months. There were no differences between groups in mortality with only four deaths (7%). Patients with CLD fared better than those with NM or CA in duration of ventilatory support, duration of tracheostomy, percentage of successful weaning from mechanical ventilation, and neurodevelopmental outcomes. Subjects with CLD had a significantly greater frequency of tracheomalacia (86%), feeding disorders (86%), and hypogammaglobulinemia G (77%). There were no differences between groups for respiratory readmissions or family dysfunction. We conclude that almost all patients with CRFIC will survive, but morbidity outcomes will vary based on the underlying diagnosis.

Chemical sclerosis of the pleural space is used to prevent recurrence of spontaneous pneumothorax. To test whether sclerosis restricts diaphragmatic excursion, we measured diaphragmatic excursion by ultrasonography in subjects with unilateral pleural sclerosis and compared it with diaphragmatic excursions in normal subjects, in subjects with cystic fibrosis (a diffuse bilateral lung disease), and in those who underwent surgical procedures that obliterate the pleural space. In five subjects with unilateral chemical sclerosis, diaphragmatic excursion was significantly less on the sclerosed side than on the contralateral side (10.7 +/- 1.3 vs 17.3 +/- 1.7 mm, mean +/- SEM; p less than .01). Compared with those of normal subjects, the side-to-side differences in excursion were increased by pulmonary disease (p less than .03) and additionally by unilateral sclerosis (p less than .015). There was no significant difference between diaphragmatic excursions on left and right sides of subjects without history of pleural disease. These data suggest that chemical pleural sclerosis causes a measurable reduction in diaphragmatic excursion on the affected side. The physiologic significance of this effect is not known.

An infant with severe combined immunodeficiency syndrome (SCIDS) secondary to adenosine deaminase deficiency had pneumonitis and combined infection with respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3). Four separate courses of ribavirin were delivered by small-particle aerosol. The PIV3 disappeared during the first course, and RSV disappeared after the fourth course on the 58th hospital day. Neither virus returned during profound immunosuppression for bone marrow transplantation. Secretory antibody to both viruses was found and may have assisted in recovery. Strains of RSV from the 9th, 15th, 29th, and 55th hospital days showed similar sensitivities to ribavirin in vitro. Ribavirin can be a useful drug in the treatment of respiratory viral infections in patients with SCIDS.